This research program proposes to study the metabolic and neurochemical basis of controlled and excessive alcohol drinking behavior in genetically and selected lines of rats that exhibit innate alcohol preference (P) and aversion or nonpreference (NP), and to develop the P-line into an animal model of alcoholism. The following correlates of alcohol preference and nonpreference will be sought by comparison of the P and the NP lines: 1) Other innate behavioral and physiological differences in brain function. 2) Innate differences in brain alcohol and acetaldehyde metabolism, alcohol and acetaldehyde dehydrogenase activity, Na ion, K ion-ATPase activity, and the content and metabolism of serotonin, norepinephrine and dopamine. The brain content of acetylcholine, gamma-aminobutyric acid, taurine and other putative amino acid neurotransmitter compounds will also be measured. 3) Differences in the acute and chronic effects of alcohol on the above. 4) Differences in the chronic effects of ethanol on liver alcohol and acetaldehyde metabolism. 5) Differences in the effect of tetrahydroisoquinoline compounds on drinking behavior. Additionally, the relative contributions of orosensory cues, the pharmacologic actions of ethanol and the caloric value of ethanol to drinking behavior will be sought. Finally, operant conditioning, scheduling of food or ethanol presentation, and/or prolonged free-choice consumption of ethanol will be examined as techniques capable of producing chronic ethanol intoxication, dependence and withdrawal in the P-line of rats.